罗格列酮和甲基泼尼松龙联合治疗大鼠脊髓损伤的实验研究

The Experiment Study of Combinative Treatment by Rosiglitazone and Methylprednisolone after Spinal Cord Injury in Rats

目的通过建立脊髓损伤动物模型,探讨甲基泼尼松龙(MP)、罗格列酮联合用药与单独用药对脊髓损伤的疗效差别。方法参照动脉瘤夹压迫法制作大鼠的脊髓损伤模型,并随机分为6组,分别为假手术组、单纯损伤组、脊髓损伤后生理盐水注射组、MP注射组、罗格列酮注射组、MP和罗格列酮联合应用治疗组。于伤后3、7、14、21、28d行神经功能评分,RT-PCR检测脊髓损伤12、24h、3、7、14、21、28d后炎性因子肿瘤坏死因子α(TNF-α)和白细胞介素1β(IL-1β)的mRNA的表达,Western-bloting法检测伤后24h凋亡相关蛋白Bax和Bcl-2的表达。结果伤后各个时间点的神经功能评分上,两药联合应用组较其他各组显著增高(P<0.01),伤后炎性因子TNF-α和IL-1β的mRNA表达方面,两药联合应用治疗后炎性因子mRNA表达均显著降低(P<0.05),脊髓损伤24h后,Bax蛋白表达升高,Bcl-2蛋白表达下降,两药联合应用组表现Bax蛋白表达下降Bcl-2蛋白表达升高更明显(P<0.05)。结论脊髓损伤后应用MP及罗格列酮治疗均有效,二者合用显示出明显的协同作用。

Objective To investigate the efficacy of combined or single use of Methylprednisolone（MP） and Rosiglitazone in the treatment of spinal cord injury in rats.Methods The rats were completely paralyzed by aneurysm clip method and randomized into six groups,which are group sham,group SCI only,group SCI and vehicle（saline）,group Methylprednisolone（MP）,group Rosiglitazone（RSG） and group combination of MP and RSG.Analysised the Basso,Beattie,Bresnahan locomotor rating scale（BBB） scores at the end of 3,7,14,28days after injury.The technique of RT-PCR had been used to calculate the mRNA expression of TNF-α and IL-1β at the time point of 12,24h,3,7,14,21,28d after operation.After 24h of SCI,the western-bloting technique had been used to monitor the expression of Bax and Bcl-2,which are apoptosis associated proteins.Result Compare with the other groups,the combinative group had the better BBB scores in every time point（P0.01）.Combination of this two drugs could reduce the expression of the mRNA of TNF-α and IL1β,and had significant difference with other groups.The expression of Bax were raised and the Bcl-2 were decreased after 24h postoperative.While the combinative group could increase the expression of Bcl-2 and decrease the Bax more apparently than other groups.Conclusion Single use one of the drugs：MP and RSG,could receive good efficacy in the treatment of SCI,but the combinative using could get much more better result,and the efficacy of one drug is cooperate with the other one.